Long-acting Cabotegravir + Rilpivirine for HIV

(ATLAS-2M Trial)

Recruiting at 114 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: ViiV Healthcare

Must be taking: Antiretrovirals

Must not be taking: Anticoagulants, Etravirine

Disqualifiers: Pregnancy, Hepatitis B, Seizures, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 4

1049 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, if you are on a standard HIV treatment, you need to have been on the same regimen for at least 6 months before joining the study. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Cabotegravir + Rilpivirine for HIV?

Research shows that the long-acting injectable combination of cabotegravir and rilpivirine is effective in maintaining HIV viral suppression, similar to traditional oral therapies. It is particularly beneficial for people who have trouble sticking to daily oral medication, as it requires less frequent dosing. ^{1 2 3 4 5}

How is the long-acting cabotegravir and rilpivirine treatment for HIV different from other treatments?

This treatment is unique because it is the first long-acting injectable option for maintaining HIV-1 viral suppression, requiring injections only every 4 to 8 weeks, unlike traditional daily oral medications. It offers a new mode of delivery that can help people who have difficulty adhering to daily pills, although it may cause injection-site reactions. ^{1 2 4 6 7}

What is the purpose of this trial?

This Antiretroviral Therapy as Long Acting Suppression every 2 Months (ATLAS-2M) study is designed to demonstrate the non-inferior antiviral activity and safety of CAB LA + RPV LA administered every 8 weeks (Q8W) compared to CAB LA + RPV LA administered every 4 weeks (Q4W) over a 48-week treatment period in approximately 1020 adult HIV-1 infected subjects. Subjects will be divided in 2 groups; Group 1 will include subjects receiving current anti-retroviral (ART) standard of care (SOC) therapy whereas group 2 will include subjects currently receiving CAB LA + RPV LA Q4W in ATLAS study. Subjects in both groups will be randomized to receive CAB LA + RPV LA Q4W or Q8W. The study will be carried out in 3 phases including screening phase, maintenance phase and extension phase. Subjects choosing not to enter the Extension phase can complete their study participation at the Week 100 visit and enter into the 52-week Long-Term Follow-Up (LTFU) Phase as required. A sub-study in the ATLAS-2M study will evaluate the pharmacokinetics, tolerability and efficacy of CAB and RPV long acting injections following intramuscular administration in the Vastus Lateralis Muscle (thigh) in HIV-infected Adult Participants who have received at least three years of Gluteal Injections in this ATLAS-2M Study.

Research Team

GSK Clinical Trials

Principal Investigator

ViiV Healthcare

Eligibility Criteria

Adults with HIV-1 who have maintained a viral load under 50 copies/mL and been on stable antiretroviral therapy for at least 6 months. Participants must understand the study commitments and be likely to complete them, not be pregnant or breastfeeding, and use effective contraception if of reproductive potential. Those with certain health conditions or taking specific medications are excluded.

Inclusion Criteria

I am not pregnant, not breastfeeding, and meet the fertility criteria.

Subjects enrolled in France must be affiliated to, or a beneficiary of, a social security category

Be considered as an appropriate candidate for participation in an investigative clinical trial with oral and intramuscularly injectable medications (e.g., no active substance use disorder, acute major organ disease, or planned long-term work assignments out of the country, etc.)

Exclusion Criteria

I need long-term blood thinners, with some exceptions.

I am allergic to the study drug or similar medications.

I don't have any health issues that would affect how my body handles the study medication.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Maintenance

Participants receive CAB LA + RPV LA every 4 or 8 weeks to evaluate efficacy, safety, and tolerability

48 weeks

Visits every 4 or 8 weeks

Extension

Participants may continue treatment beyond the main study period

Up to Week 100

Long-Term Follow-Up

Participants are monitored for safety and effectiveness after treatment

52 weeks

Treatment Details

Interventions

• Cabotegravir Injectable Suspension
• Cabotegravir Tablets
• Rilpivirine Injectable Suspension
• Rilpivirine Tablets

Trial Overview The trial is testing the effectiveness of long-acting injections of Cabotegravir plus Rilpivirine given every two months compared to every month in controlling HIV-1. It includes adults previously treated with standard care or those already receiving these drugs monthly, assessing safety over a year.

Participant Groups

Group I: Subjects in group 2 receiving study treatment once in 8 weeks Experimental Treatment 2 Interventions

Group 2 will consist of subjects currently receiving CAB LA + RPV LA Q4W in ATLAS study. Subjects in Group 2 will be randomized to receive CAB LA plus RPV LA Q8W via IM route.

Group II: Subjects in group 2 receiving study treatment once in 4 weeks Experimental Treatment 2 Interventions

Group 2 will consist of subjects currently receiving CAB LA + RPV LA Q4W in ATLAS study. Subjects in Group 2 will be randomized to continue CAB LA plus RPV LA Q4W administration via IM route.

Group III: Subjects in group 1 receiving study treatment once in 8 weeks Experimental Treatment 4 Interventions

Group 1 will consist of subjects randomized from current ART SOC therapy. Subjects in group 1 will be randomized to receive CAB LA plus RPV LA Q8W via IM route. All subjects will receive oral therapy with CAB 30 mg + RPV 25 mg once daily prior to randomization.

Group IV: Subjects in group 1 receiving study treatment once in 4 weeks Experimental Treatment 4 Interventions

Group 1 will consist of subjects randomized from current ART SOC therapy. Subjects in group 1 will be randomized to receive CAB LA plus RPV LA Q4W via intramuscular (IM) route. All subjects will receive oral therapy with CAB 30 mg + RPV 25 mg once daily prior to randomization.

Who Is Running the Clinical Trial?

ViiV Healthcare

Lead Sponsor

Trials

379

Recruited

479,000+

Founded

2009

Headquarters

London, England, UK

Known For

HIV Research

Top Products

- Tivicay (dolutegravir), - Triumeq (abacavir/dolutegravir/lamivudine), - Juluca (dolutegravir/rilpivirine), - Apretude (cabotegravir)

Dr. Harmony Garges

ViiV Healthcare

Chief Medical Officer

MD

Deborah Waterhouse

ViiV Healthcare

Chief Executive Officer since 2017

Bachelor's degree in Business Administration

Janssen Research & Development, LLC

Industry Sponsor

Trials

1,022

Recruited

6,408,000+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

Janssen Research and Development

Collaborator

Trials

2

Recruited

1,200+

Findings from Research

Cabotegravir and rilpivirine, as long-acting injectable therapy for HIV-1, have shown to be non-inferior to traditional oral triple-therapy in phase II and III trials, indicating their effectiveness as a treatment option.

Patients generally accept the 4-weekly or 8-weekly injections despite some experiencing injection-site reactions, but there are still important questions regarding missed doses, drug interactions, and the therapy's efficacy across different HIV-1 subtypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating cabotegravir/rilpivirine long-acting, injectable in the treatment of HIV infection: emerging data and therapeutic potential. Fernandez, C., van Halsema, CL.[2020]

Long-acting injectable cabotegravir-rilpivirine (CAB-RPV) significantly improves viral suppression rates in people with HIV who have adherence challenges, achieving 60% suppression at 3 months compared to only 13% with standard oral treatment.

In a model projecting outcomes over 3 years, CAB-RPV combined with supportive services is expected to lead to a 44% viral suppression rate and a life expectancy of 9.4 years, outperforming both standard oral treatments and those with additional support services.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Projected Benefits of Long-Acting Antiretroviral Therapy in Nonsuppressed People With Human Immunodeficiency Virus Experiencing Adherence Barriers. Chen, W., Gandhi, M., Sax, PE., et al.[2023]

In a Phase 2b study involving 97 adults living with HIV-1, the long-acting formulation of cabotegravir and rilpivirine (CAB+RPV) administered every 2 months successfully maintained virologic suppression, with no participants showing HIV-1 RNA levels above 50 copies/ml after 12 months.

The long-acting CAB+RPV treatment had a favorable safety profile, with no new safety concerns identified, and 88% of participants preferred this regimen over their previous daily oral treatment, indicating high treatment satisfaction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-acting cabotegravir and rilpivirine for HIV-1 suppression: switch to 2-monthly dosing after 5 years of daily oral therapy. Mills, A., Richmond, GJ., Newman, C., et al.[2023]

Long-acting injectable therapies, cabotegravir (CAB) and rilpivirine (RPV), have been shown to be as effective as traditional oral antiretroviral therapy (ART) for HIV-1, maintaining efficacy over 96 weeks in clinical trials with virologically suppressed adults.

CAB has also demonstrated effectiveness as a preexposure prophylaxis (PrEP) option, significantly reducing HIV infections compared to daily oral medication, indicating its potential for broader use in HIV prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new paradigm for antiretroviral delivery: long-acting cabotegravir and rilpivirine for the treatment and prevention of HIV. Bares, SH., Scarsi, KK.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Long-acting intramuscular cabotegravir and rilpivirine in adults with HIV-1 infection (LATTE-2): 96-week results of a randomised, open-label, phase 2b, non-inferiority trial. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Evaluating cabotegravir/rilpivirine long-acting, injectable in the treatment of HIV infection: emerging data and therapeutic potential. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Projected Benefits of Long-Acting Antiretroviral Therapy in Nonsuppressed People With Human Immunodeficiency Virus Experiencing Adherence Barriers. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

The New Era of Long-Acting Antiretroviral Therapy: When and Why to Make the Switch. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Long-acting cabotegravir and rilpivirine for HIV-1 suppression: switch to 2-monthly dosing after 5 years of daily oral therapy. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

A new paradigm for antiretroviral delivery: long-acting cabotegravir and rilpivirine for the treatment and prevention of HIV. [2023]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy, safety, and tolerability of switching to long-acting cabotegravir plus rilpivirine versus continuing fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide in virologically suppressed adults with HIV, 12-month results (SOLAR): a randomised, open-label, phase 3b, non-inferiority trial. [2023]